It is well documented that glycolysis provides the energy requirements to the lymphocyte during lymphoblast transformation. Changes in carbohydrate metabolism can be measured as early as 15 minutes after the addition of mitogen, and the blocking of glycolysis totally prevents blastogenesis. Previous studies in our laboratory have revealed a number of dramatic changes in glycolytic enzyme levels and isozyme patterns which appear to be required for blastogenesis. It has been clearly shown that the failure of lymphocytes from senescent individuals to respond to mitogenic or antigenic stimuli is due to an intrinsic defect in the lymphocyte, and preliminary evidence suggests that at least some of these requisite adaptations in carbohydrate metabolism may be altered. The proposed investigation seeks to fully describe the genetic and apogenetic bases by which these enzyme adaptations occur during blastogenesis in lymphocytes from young and senescent populations. The study will also assess overall effects on carbohydrate metabolism by monitoring changes in the adenylate charge and redox state of the cells during this adaptation. The production of enzymes with altered catalytic, regulatory, stability or immunological activity will be monitored during blastogenesis of cells from young and old populations. The rates of synthesis, degradation and the half-lives of the enzymes will also be measured. It is believed that these studies will not only identify the critical regulatory responses required for normal lymphocyte activation, but may also provide clues as to how these responses are altered by the aging process.